University of Hertfordshire

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Ablation of AMP-activated protein kinase alpha1 and alpha2 from mouse pancreatic beta cells and RIP2.Cre neurons suppresses insulin release in vivo. / Sun, G; Tarasov, A I; McGinty, J; McDonald, A; da Silva Xavier, G; Gorman, T; Marley, A; French, P M; Parker, H; Gribble, F; Reimann, F; Prendiville, O; Carzaniga, R; Viollet, B; Leclerc, I; Rutter, G A.

In: Diabetologia, Vol. 53, No. 5, 05.2010, p. 924-36.

Research output: Contribution to journalArticlepeer-review

Harvard

Sun, G, Tarasov, AI, McGinty, J, McDonald, A, da Silva Xavier, G, Gorman, T, Marley, A, French, PM, Parker, H, Gribble, F, Reimann, F, Prendiville, O, Carzaniga, R, Viollet, B, Leclerc, I & Rutter, GA 2010, 'Ablation of AMP-activated protein kinase alpha1 and alpha2 from mouse pancreatic beta cells and RIP2.Cre neurons suppresses insulin release in vivo', Diabetologia, vol. 53, no. 5, pp. 924-36. https://doi.org/10.1007/s00125-010-1692-1

APA

Sun, G., Tarasov, A. I., McGinty, J., McDonald, A., da Silva Xavier, G., Gorman, T., Marley, A., French, P. M., Parker, H., Gribble, F., Reimann, F., Prendiville, O., Carzaniga, R., Viollet, B., Leclerc, I., & Rutter, G. A. (2010). Ablation of AMP-activated protein kinase alpha1 and alpha2 from mouse pancreatic beta cells and RIP2.Cre neurons suppresses insulin release in vivo. Diabetologia, 53(5), 924-36. https://doi.org/10.1007/s00125-010-1692-1

Vancouver

Author

Sun, G ; Tarasov, A I ; McGinty, J ; McDonald, A ; da Silva Xavier, G ; Gorman, T ; Marley, A ; French, P M ; Parker, H ; Gribble, F ; Reimann, F ; Prendiville, O ; Carzaniga, R ; Viollet, B ; Leclerc, I ; Rutter, G A. / Ablation of AMP-activated protein kinase alpha1 and alpha2 from mouse pancreatic beta cells and RIP2.Cre neurons suppresses insulin release in vivo. In: Diabetologia. 2010 ; Vol. 53, No. 5. pp. 924-36.

Bibtex

@article{e570d79c4142468197979f52c857cf10,
title = "Ablation of AMP-activated protein kinase alpha1 and alpha2 from mouse pancreatic beta cells and RIP2.Cre neurons suppresses insulin release in vivo",
abstract = "AIMS/HYPOTHESIS: AMP-activated protein kinase (AMPK) is an evolutionarily conserved enzyme and a target of glucose-lowering agents, including metformin. However, the precise role or roles of the enzyme in controlling insulin secretion remain uncertain.METHODS: The catalytic alpha1 and alpha2 subunits of AMPK were ablated selectively in mouse pancreatic beta cells and hypothalamic neurons by breeding Ampkalpha1 [also known as Prkaa1]-knockout mice, bearing floxed Ampkalpha2 [also known as Prkaa2] alleles (Ampkalpha1 ( -/- ),alpha2( fl/fl ),), with mice expressing Cre recombinase under the rat insulin promoter (RIP2). RIP2 was used to express constitutively activated AMPK selectively in beta cells in transgenic mice. Food intake, body weight and urinary catecholamines were measured using metabolic cages. Glucose and insulin tolerance were determined after intraperitoneal injection. Beta cell mass and morphology were analysed by optical projection tomography and confocal immunofluorescence microscopy, respectively. Granule docking, insulin secretion, membrane potential and intracellular free Ca(2+) were measured with standard techniques.RESULTS: Trigenic Ampkalpha1 ( -/- ),alpha2( fl/fl ) expressing Cre recombinase and lacking both AMPKalpha subunits in the beta cell, displayed normal body weight and increased insulin sensitivity, but were profoundly insulin-deficient. Secreted catecholamine levels were unchanged. Total beta cell mass was unaltered, while mean islet and beta cell volume were reduced. AMPK-deficient beta cells displayed normal glucose-induced changes in membrane potential and intracellular free Ca(2+), while granule docking and insulin secretion were enhanced. Conversely, betaAMPK transgenic mice were glucose-intolerant and displayed defective insulin secretion.CONCLUSIONS/INTERPRETATION: Inhibition of AMPK activity within the beta cell is necessary, but not sufficient for stimulation of insulin secretion by glucose to occur. AMPK activation in extrapancreatic RIP2.Cre-expressing cells might also influence insulin secretion in vivo.",
keywords = "AMP-Activated Protein Kinases/genetics, Analysis of Variance, Animals, Blood Glucose/metabolism, Body Weight/genetics, Dietary Fats, Eating/genetics, Electrophysiology, Fluorescent Antibody Technique, Glucose Tolerance Test, Hyperglycemia/genetics, Hypothalamus/metabolism, Insulin/genetics, Insulin-Secreting Cells/metabolism, Mice, Mice, Knockout, Neurons/metabolism, Promoter Regions, Genetic/genetics, Rats",
author = "G Sun and Tarasov, {A I} and J McGinty and A McDonald and {da Silva Xavier}, G and T Gorman and A Marley and French, {P M} and H Parker and F Gribble and F Reimann and O Prendiville and R Carzaniga and B Viollet and I Leclerc and Rutter, {G A}",
year = "2010",
month = may,
doi = "10.1007/s00125-010-1692-1",
language = "English",
volume = "53",
pages = "924--36",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "5",

}

RIS

TY - JOUR

T1 - Ablation of AMP-activated protein kinase alpha1 and alpha2 from mouse pancreatic beta cells and RIP2.Cre neurons suppresses insulin release in vivo

AU - Sun, G

AU - Tarasov, A I

AU - McGinty, J

AU - McDonald, A

AU - da Silva Xavier, G

AU - Gorman, T

AU - Marley, A

AU - French, P M

AU - Parker, H

AU - Gribble, F

AU - Reimann, F

AU - Prendiville, O

AU - Carzaniga, R

AU - Viollet, B

AU - Leclerc, I

AU - Rutter, G A

PY - 2010/5

Y1 - 2010/5

N2 - AIMS/HYPOTHESIS: AMP-activated protein kinase (AMPK) is an evolutionarily conserved enzyme and a target of glucose-lowering agents, including metformin. However, the precise role or roles of the enzyme in controlling insulin secretion remain uncertain.METHODS: The catalytic alpha1 and alpha2 subunits of AMPK were ablated selectively in mouse pancreatic beta cells and hypothalamic neurons by breeding Ampkalpha1 [also known as Prkaa1]-knockout mice, bearing floxed Ampkalpha2 [also known as Prkaa2] alleles (Ampkalpha1 ( -/- ),alpha2( fl/fl ),), with mice expressing Cre recombinase under the rat insulin promoter (RIP2). RIP2 was used to express constitutively activated AMPK selectively in beta cells in transgenic mice. Food intake, body weight and urinary catecholamines were measured using metabolic cages. Glucose and insulin tolerance were determined after intraperitoneal injection. Beta cell mass and morphology were analysed by optical projection tomography and confocal immunofluorescence microscopy, respectively. Granule docking, insulin secretion, membrane potential and intracellular free Ca(2+) were measured with standard techniques.RESULTS: Trigenic Ampkalpha1 ( -/- ),alpha2( fl/fl ) expressing Cre recombinase and lacking both AMPKalpha subunits in the beta cell, displayed normal body weight and increased insulin sensitivity, but were profoundly insulin-deficient. Secreted catecholamine levels were unchanged. Total beta cell mass was unaltered, while mean islet and beta cell volume were reduced. AMPK-deficient beta cells displayed normal glucose-induced changes in membrane potential and intracellular free Ca(2+), while granule docking and insulin secretion were enhanced. Conversely, betaAMPK transgenic mice were glucose-intolerant and displayed defective insulin secretion.CONCLUSIONS/INTERPRETATION: Inhibition of AMPK activity within the beta cell is necessary, but not sufficient for stimulation of insulin secretion by glucose to occur. AMPK activation in extrapancreatic RIP2.Cre-expressing cells might also influence insulin secretion in vivo.

AB - AIMS/HYPOTHESIS: AMP-activated protein kinase (AMPK) is an evolutionarily conserved enzyme and a target of glucose-lowering agents, including metformin. However, the precise role or roles of the enzyme in controlling insulin secretion remain uncertain.METHODS: The catalytic alpha1 and alpha2 subunits of AMPK were ablated selectively in mouse pancreatic beta cells and hypothalamic neurons by breeding Ampkalpha1 [also known as Prkaa1]-knockout mice, bearing floxed Ampkalpha2 [also known as Prkaa2] alleles (Ampkalpha1 ( -/- ),alpha2( fl/fl ),), with mice expressing Cre recombinase under the rat insulin promoter (RIP2). RIP2 was used to express constitutively activated AMPK selectively in beta cells in transgenic mice. Food intake, body weight and urinary catecholamines were measured using metabolic cages. Glucose and insulin tolerance were determined after intraperitoneal injection. Beta cell mass and morphology were analysed by optical projection tomography and confocal immunofluorescence microscopy, respectively. Granule docking, insulin secretion, membrane potential and intracellular free Ca(2+) were measured with standard techniques.RESULTS: Trigenic Ampkalpha1 ( -/- ),alpha2( fl/fl ) expressing Cre recombinase and lacking both AMPKalpha subunits in the beta cell, displayed normal body weight and increased insulin sensitivity, but were profoundly insulin-deficient. Secreted catecholamine levels were unchanged. Total beta cell mass was unaltered, while mean islet and beta cell volume were reduced. AMPK-deficient beta cells displayed normal glucose-induced changes in membrane potential and intracellular free Ca(2+), while granule docking and insulin secretion were enhanced. Conversely, betaAMPK transgenic mice were glucose-intolerant and displayed defective insulin secretion.CONCLUSIONS/INTERPRETATION: Inhibition of AMPK activity within the beta cell is necessary, but not sufficient for stimulation of insulin secretion by glucose to occur. AMPK activation in extrapancreatic RIP2.Cre-expressing cells might also influence insulin secretion in vivo.

KW - AMP-Activated Protein Kinases/genetics

KW - Analysis of Variance

KW - Animals

KW - Blood Glucose/metabolism

KW - Body Weight/genetics

KW - Dietary Fats

KW - Eating/genetics

KW - Electrophysiology

KW - Fluorescent Antibody Technique

KW - Glucose Tolerance Test

KW - Hyperglycemia/genetics

KW - Hypothalamus/metabolism

KW - Insulin/genetics

KW - Insulin-Secreting Cells/metabolism

KW - Mice

KW - Mice, Knockout

KW - Neurons/metabolism

KW - Promoter Regions, Genetic/genetics

KW - Rats

U2 - 10.1007/s00125-010-1692-1

DO - 10.1007/s00125-010-1692-1

M3 - Article

C2 - 20221584

VL - 53

SP - 924

EP - 936

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 5

ER -